1. Field of the Invention
The invention relates to an implant and to a process for producing it.
2. Related Prior Art
Implants, and processes for producing them, have been frequently disclosed in the prior art.
Implantable structures in combination with cells are used, in particular, in the field of tissue engineering, an interdisciplinary field of research which is concerned with methods and materials for producing “artificial” tissue and organ systems. Thus, it is possible to use artificially produced implants as, for example, replacements for skin, bone, cartilage, lenses or as vascular grafts.
In vascular surgery, small-lumen implants are used, in particular, when it is not possible to use a patient's own blood vessels. This is the case, for example, when a specific blood vessel length is required or when the autologous blood vessels cannot be used because of their pathophysiological properties. In this connection, use is made of vascular grafts made of synthetic material, with use being made, in particular, of synthetic materials such as knitted threads of polyethylene terephthalate (PET), (trade name: Dacron), or of expanded polytetrafluoroethylene (ePTFE).
Preference is given to using vascular grafts made out of these synthetic materials since they possess advantageous structural and biocompatible properties. Thus, surrounding tissue can ingrow, on the one hand, and, on the other hand, no blood plasma may escape through the pores. In the case of the ePTFE implants, this is achieved by the adjusted size of the pores, whereas knitted PET implants are impregnated by being coated with resorbable material, such as collagen or gelatin. After implantation, the coating is resorbed to the extent that the surrounding, newly formed tissue grows into the porous collagen layer.
If use is made of synthetic materials which are one-sidedly collagen-coated on the outside, there is a great danger, for example in the case of small-lumen vascular grafts, that the exposed foreign surface of the internal lumen will induce blood coagulation and that the implanted vessel will very rapidly become occluded. This is because the coagulation system, the complement system and the immune system can be activated, in particular, by slowly flowing blood coming into contact with synthetic surfaces.
Consequently, prostheses of this nature cannot be used in the small-lumen vessel range (φ<6 mm) since, in this range, there is a danger of the vessel rapidly becoming occluded.
More advanced approaches to avoiding blood coagulation are directed towards colonizing the coated implants with cells, such as endothelial cells or fibroblasts.
Endothelial cells line the surface of human blood vessels. Seeding the lumen of vascular grafts with endothelial cells presents the flowing blood with a surface whose coagulation-activating and complement-activating properties are markedly reduced. Coculturing vascular grafts with fibroblasts and endothelial cells, as demonstrated, for example, in PCT 98/01782, improves the ability of the implant to grow into the surrounding tissue and stabilizes the endothelial cell layer in the internal lumen.
Consequently, the interaction of the various cell types which are present, for example, in natural vessels is of importance for the ability of the implants to function. In addition to a high degree of biocompatibility, care must also be taken to ensure that the structure of the implant is adapted to the requirements of different cells.
Another developmental approach is to use acellularized blood vessels of animal origin. In U.S. Pat. No. 5,899,936, these vessels are seeded, after their cellular components have been removed, with autologous cells and then implanted.
A particular disadvantage of these developments is the fact that the implants cannot be produced such that they are adapted to the patient but, instead, are predetermined by the donor animal with regard to the length and size of the vessel. Furthermore, the risks of a disease being transferred by viruses or prions by way of such tissues are not completely resolved.
Another disadvantage is that it is not possible to embed an additional supporting structure into an implant which has been produced in this way in order to increase its stability. In addition, acellularized structures are only relatively storable. Furthermore, the latest debate in the field of xenotransplants indicates that technically produced vascular grafts are preferred.
Recent experimental approaches are directed towards developing completely resorbable implants which are made of synthetic materials such as polyglycolic acid or polylactide. In the context of wound healing, these synthetic materials are replaced with endogenous tissue. An advantage of these implants is that the materials regenerate completely and no synthetic materials, which can give rise to infections, remain in the body. Disadvantages of these implants are the impairment of cell growth during resorption, e.g. as the result of a shift in pH when the polylactide is degraded, and the difficulty in controlling the formation of new tissue, since premature resorption can lead to the implant failing.
WO 00/47129 discloses a method for using a master plate to produce a resorbable membrane which possesses a three-dimensional structure. In this connection, the membrane can also be made of non-resorbable synthetic materials and be coated, where appropriate, with a protein matrix.
This method suffers from the disadvantage that the production of the membrane having a three-dimensional structure is very elaborate. Thus, it is first of all necessary to make the master plates for the different membranes which are required in each case before the supporting structure itself can be produced.
U.S. Pat. No. 4,787,900 discloses a method in which an inner structure made of a resorbable material is coated with an outer layer composed of a material which can also be degraded. At the same time, the two layers can in each case be seeded with cells. A disadvantage of this method is the fact that it is not possible to adapt the outer structure to the particular requirements of the environment into which it is to be implanted. In addition, elaborate steps are involved in the production of the outer layer in this method since, after a freeze-drying process, the outer structure has first of all to be cut back to the desired layer thickness, something which leads to a substantial consumption of material.
Consequently, special mechanical and structural demands are made on implants. Thus, in addition to having adequate structural stability, they must also possess strength and stretching properties which match the tissue which is to be replaced. In addition, implants have to exhibit a variety of fits, lengths and diameters. Furthermore, the microstructuring, such as the inner pore structure, is of importance for seeding with cells and for ingrowing tissue. In addition, the implants should be characterized by the fact that they do not induce any immunological allergies or reactions and by the fact that they are optimally adapted to the particular tissue into which they are implanted.